Lab Notes: Potential Target ID'd in ALS

by MedPage Today Staff

A previously unknown protein builds up in the brains of patients with amyotrophic lateral sclerosis and frontotemporal dementia, offering a new treatment target. Also this week: rats learn to feel light.

Protein May be ALS Therapy Target

People with amyotrophic lateral sclerosis (often called Lou Gehrig's disease) and frontotemporal dementia have no effective treatment options for the devastating diseases. Now researchers led by Leonard Petrucelli, PhD, of the Mayo Clinic in Jacksonville, Fla., think they may have found a potential therapeutic target for both.

Analysis of brain tissue from people with the illnesses – now recognized as part of a continuum of disease – found a build-up of an abnormal protein, which they called C9RANT. It's generated, they reported in Neuron, as a result of repeated expansions of nucleotides in the noncoding region of the C9ORF72 gene, linked to both diseases.

The C9RANT protein is large and insoluble, which raises the possibility that – like the tau protein in Alzheimer's disease – it causes cell death or toxicity, the researchers noted. "Our discovery offers a potential target to prevent neuronal loss in patients carrying the C9ORF72 repeat expansion," Petrucelli said in a statement.

The protein can also be detected in the cerebrospinal fluid of patients, suggesting it might be useful both for diagnosis and prognosis, the researchers argued.

-- Michael Smith

Rats Gain a Sixth Sense

Rats fitted with an infrared detector wired to the brain area that processes touch sensations from their whiskers learned to "feel" infrared light, researchers reported in Nature Communications.

Most neuroprosthetic devices have been designed to replace a damaged sense, such as cochlear implants for hearing loss. But experiments led by Miguel Nicolelis, MD, PhD, of Duke University, demonstrated that it was possible to augment the sensory capacity of intact animals.

The researchers trained a group of rats to respond to cortical microstimulation by seeking a portal emitting infrared light, sweeping their heads to detect the light source, where they would be given a sip of water. This pseudovision took place without hijacking the sensory capabilities of the animals' whiskers, which retained the ability to respond to touch.

The researchers suggested that these findings could translate into a new generation of far more sensitive prosthetic limbs in humans, utilizing a "brain-machine-brain" interaction.

-- Nancy Walsh

Possible New Approach for Treating Atherosclerosis

An enzyme involved in the development of atherosclerotic plaques may represent a future therapeutic target for patients with coronary artery disease, researchers found.

Previous studies have shown an association between the ADAMTS7 gene and risk of coronary artery disease. The ADAMTS7 enzyme breaks down a structural protein in the arterial wall called thrombospondin-5, a process that allows cells in the arterial wall to more easily move into and enlarge atherosclerotic plaques. A previous study in rats confirmed that degradation of thrombospondin-5 promoted atherosclerosis after a vascular mechanical injury.

A variant of ADAMTS7, however, has been associated with a reduced risk of coronary artery disease. Shu Ye, PhD, of Queen Mary University of London, and colleagues explored the underlying mechanism.

Using data from a prior study that included 787 Italian participants, the researchers discovered that ADAMTS7 is found in smooth muscle cells in coronary and carotid atherosclerotic plaques. They confirmed that a variant of the enzyme was associated with a reduced risk of atherosclerosis and less severe atherosclerotic plaques.

As the researchers reported in the American Journal of Human Genetics, in vitro studies revealed the underlying mechanism: individuals with the ADAMTS7 variant were less able to break down thrombospondin-5 in the arterial wall.

-- Todd Neale

Statins in Pregnancy

Preeclampsia creates problems for fetal development, but pravastatin (Pravachol) may help reverse the long-term consequences, a mouse study suggested.

Researchers from the University of Texas Medical Branch in Galveston gave pregnant mice with preeclampsia the statin or plain water as a control.

When the pups reached adulthood, prenatal exposure to pravastatin appeared to have prevented the hypertension seen in control group males and the cardiovascular relaxation abnormalities seen in both sexes in the control group.

Mice born from preeclampsic mothers that didn't take the statin were also more clumsy and slower to perform motor skill tests as adults than those with prenatal pravastatin exposure.

"Maternal therapy with pravastatin prevents this altered developmental programming in this animal model of preeclampsia," the group concluded.

The findings were presented this week at the Society for Maternal-Fetal Medicine in San Francisco. A pilot human trial is underway.

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